Medical Treatment of Vertigo

What are Medical Treatments of Vertigo?

Vestibular suppressant and antiemetic drugs are the mainstay of treatment of vertigo. In addition, there are a number of new medical treatments that have either not been proved effective in clinical trials or are otherwise controversial.

Vestibular Suppressant

Vestibular suppressants, generally speaking, are drugs that reduce nystagmus (eye movements) caused by a vestibular imbalance, or drugs that reduce motion sickness. Table 1 lists commonly used vestibular suppressants in order of preference. These drugs fall into three major groups: anticholinergics, antihistamines, and benzodiazepines.

Table 1 Vestibular Suppressant

Drug

Dose

Adverse Reactions

Precautions

Pharmacologic Class

Meclizine (Antivert, Bonine)

25 mg q 4-6h

sedating

anticholinergic precautions if prostatic enlargement

antihistamine

Lorazepam (Ativan)

0.5 mg BID

mildly sedating

drug dependency

benzodiazepine

Clonazepam (Klonopin)

0.5 mg BID

mildly sedating

drug dependency

benzodiazepine

Dimenhydrinate (Dramamine)

50 mg q 4-6h

same as Meclizine

anticholinergic

antihistamine

Diazepam (Valium)

2 bid PO5 mg IV (1 dose)

sedating

drug dependency; precaution in glaucoma

benzodiazepine

Amitriptyline (Elavil)

10-50 hs

sedating, in overdose cardiac arrhythmia

anticholinergic tricyclic antihistamine

Doses are all those used routinely for adults, and will generally not be appropriate for children.

Anticholinergics

Anticholinergics affect muscarinic receptors and increase motion tolerance. Anticholinergics also affect compensation, producing a reversible overcompensation if administered after compensation has been attained to a vestibular imbalance (Zee, 1988). Agents with central anticholinergic effects are most important in treating vertigo, since anticholinergic drugs that do not cross the blood-brain barrier are ineffective in controlling motion sickness (Takeda et al, 1989). Unlike antihistamines, pure anticholinergics are ineffective if administered after symptoms have already appeared.

All anticholinergics used in the management of vertigo have prominent side effects of dry mouth, dilated pupils, and sedation. Scopolamine and atropine are nonspecific muscarinic receptor antagonists (Barton et al, 1994). It is to be hoped that agents selective for vestibular subtypes of muscarinic receptors will eventually be developed or discovered among our presently available pharmacopoeia, as these agents may provide vestibular suppression with fewer side effects.

Glycopyrrolate and zamifenacin are anticholinergics that have proven successful in the treatment of vertigo in small clinical trials, but more research is needed before they will become widely used (Zajonc, 2006).

Antihistamines

Antihistamines prevent motion sickness and reduce the severity of its symptoms, even if taken after the onset of symptoms (Takeda et al, 1989). All the antihistamines in general use for control of vertigo also have anticholinergic activity. With the possible exception of astemizole (Hismanal) in Meniere’s disease (Turner and Jackson, 1989), antihistamines that do not cross the blood-brain barrier are not used to control vertigo. Unfortunately, astemizole does not appear to be generally useful as it is ineffective in preventing motion sickness (Kohl et al, 1987) and because it has significant potential toxicity.

Benzodiazepines

Benzodiazepines are gamma-amino butyric acid (GABA) modulators, acting centrally to suppress vestibular responses. In small doses, these drugs are extremely useful. Addiction, impaired memory, increased risk of falling, and impaired vestibular compensation are their main shortcomings. Lorazepam is a particularly useful agent because of its effectiveness and simple kinetics. Addiction, the biggest problem, can usually be avoided by keeping the dose to 0.5 mg BID or less. Similarly, low doses of diazepam (Valium) (2 mg) can be quite effective. Clonazepam (Klonopin), appears as effective a vestibular suppressant as lorazepam. The author prefers to avoid use of alprazolam (Xanax) for vestibular suppression, because of the potential for a difficult withdrawal syndrome. Long acting benzodiazepines are not helpful for relief of vertigo. Peracitam is a derivative of GABA that has a wide range of neurological effects, including relief of vertigo (Winbald, 2005).

Antiemetics

Table 2 lists the drugs that are commonly used for control of nausea in vertiginous patients. Relatively new are the 5HT3 agents (Zofran, Kytril). In theory, these agents might not be ideal for emesis related to vestibular imbalance. The choice of agent depends mainly on considerations of the route of administration and the side effect profile. The oral agents are used for mild nausea. Suppositories are commonly used in outpatients who are unable to absorb oral agents because of gastric atony or vomiting. Injectables are used in the emergency room or inpatient settings. The new agents are used when all else fails.

Some antihistamines commonly used as vestibular suppressants have significant antiemetic properties (for example, meclizine). When an oral agent is appropriate, this agent is generally the first to be used, because it rarely causes adverse effects any more severe than drowsiness. Phenothiazines, such as prochlorperazine (Compazine) and promethazine (Phenergan), are effective antiemetics, probably because of their dopamine blocking activity, but they also act at other sites. For example, promethazine is also an H1 blocker. Because these drugs can induce significant side effects, such as dystonia, they are considered second-line drugs whose use should be brief and cautious.

Table 2: Antiemetics

Drug

Usual Dose (Adults)

Adverse Reactions

Pharmacologic Class

granisetron (Kytril)

1 mg PO BID 10 ug/kg IV daily

headache; sedation

5HT3 antagonist

meclizine (Antivert, Bonine)

12.5-25 mg q4-6h PO

sedating; precautions in glaucoma; prostate enlargement

antihistamine anticholinergic

metoclopramide(Reglan)

10 mg PO TID or 10 mg IM

restlessness or drowsiness; extrapyramidal

dopamine antagonist stimulates upper gastrointestinal motility

ondansetron (Zofran)

4-8 mg PO TID32 mg IV one dose

precaution in hepatic dysfunction

5HT3 antagonist

perphenazine (Trilafon)

2 – 4 mg PO, up to QID or 5 mg IM, up to TID

sedating extrapyramidal

phenothiazine

prochlorperazine (Compazine)

5 mg or 10 mg IM or PO q6-8 hr.25 rectal q12h

sedating extrapyramidal

phenothiazine

promethazine (Phenergan)

12.5 mg PO q6-8h or 12.5 mg IM q 6-8h

sedating extrapyramidal

phenothiazine

trimethobenzamide (Tigan)

200 mg IM TID

extrapyramidal sedating

similar to phenothiazine

thiethylperazine (Torecan)

10 mg PO, up to TID or 2 ml IM, up to TID

sedating extrapyramidal

phenothiazine

Doses are all those used routinely for adults, and will generally not be appropriate for children.

Drugs that speed gastric emptying, such as metoclopramide (Reglan) and powdered ginger root may be helpful in managing emesis (Grontved et al, 1988). Metoclopramide, a dopamine antagonist and a potent central antiemetic, is ineffective in preventing motion sickness (Kohl, 1987). Domperidone (Motilium) is an antiemetic that does not cross the blood-brain barrier and thus has less side effects.

There is a possible role for new antiemetics which are a 5-HT3 antagonists (ondansetron:Zofran; granisetron: Kytril) used in treating the nausea associated with chemotherapy and post-operative nausea and vomiting. The high cost of these agents presently limits their usefulness in the treatment of vertigo, but they are reasonable agents to try in situations where the more usual agents are ineffective or contraindicated. These agents do not appear to be helpful in preventing motion sickness (Stott et al, 1989). In theory, these agents might be less effective for vestibular elicited emesis than agents with other pharmacologic actions.

New or Unproven Treatments

Calcium Channel Blockers

Calcium channel blockers are the most promising agents in this group. More detail about these drugs can be found here. Calcium channel blockers, such as flunarizine and cinnarizine, are popular antivertiginous agents outside of the U.S. (Rascol et al, 1989). Some calcium channel blockers, such as verapamil, have quite strong constipating effects, which may be helpful in managing diarrhea caused by vestibular imbalance. However, calcium channel blockers often have anticholinergic and/or antihistaminic activity and the relative importance of calcium channel blocking associated activity for vestibular suppression has not been determined (Rascol et al, 1989).

Another problem is that almost all antihistamines have calcium-entry blocking capacity and/or calmodulin blocking properties, making it difficult to ascertain the mechanism of action (Timmerman, 1994). Calcium channel blockers may be effective in “vestibular Meniere’s disease,” or benign recurrent vertigo, as persons with these diagnoses have a high prevalence of migraine (Rassekh and Harker, 1992), for which calcium channel blockers can be very effective. The author has found daily verapamil to be helpful in a roughly one-third of patients with Meniere’s disease, causing amelioration or suppression of attacks as long as a reasonable dose is taken. This use of verapamil for vertigo has not been studied or approved in the U.S. Nimodipine, however, has recently been reported to be effective as prophylaxis of Meniere’s disease.

Sodium Channel Blockers

A sodium channel blocker, phenytoin (Dilantin), has also been recently reported to be protective against motion sickness (Knox et al, 1994). The author of this review has had no success in limited trials in patients with severe motion sickness unresponsive to the usual agents. Gabapentin (Neurontin). oxcarbamazepine (Trileptal) and carbamazepine (Tegretol) are also sometimes successfully used in treatment of vertigo, although their use has not been studied extensively. Gabapentin has also been successfully used to suppress certain types of central nystagmus (Stahl et al, 1995). Since these agents affect GABA, which is important in vertigo, an antivertigo effect is reasonable. Recent agents have been developed for epilepsy which are glutamate antagonists, but at this writing, they have not been tried as treatments of vertigo. Anticonvulsants are also promising agents for treatment of vertigo.

Another GABA agonist, baclofen (Lioresal), has shown some promise in reducing vestibular asymmetry. No human trials have yet been undertaken. This agent might be suitable for patients with uncompensated vestibular asymmetries.

Histamine Agonists

This is an interesting group that presently appears poised to move from the uncertain role category to the more conventional category. Whereas the antihistamines used in treating vertigo are usually centrally acting histamine H1-receptor antagonists, in some parts of the world an H1+H2-receptor agonist (and possibly H3 antagonist ), Serc (betahistine), is used. According to Timmerman (quoting Laurikainen), H1 receptors do not appear to be important at all in vestibular function and the antivertiginous effects of antihistamines are mediated either through non-H1 receptors or other effects of the drugs. Also, the H1 (and H2) effects are rather minor. Accordingly, Serc’s effects might occur through H2 agonism or H3 antagonism (Timmerman, 1994). H3 is an autoreceptor that modulates H1 and H2 as well as potentially other neurotransmitter systems. Thus, an agent that primarily affected H3, could at this writing, essentially, pharmacologically do anything. The pharmacological literature is confusing as some authors suggest that betahistine is an H3 agonist (Kingma, 1997) rather than an antagonist (Timmerman, 1994).

Pragmatically, a betahistine dose of 8 mg three times per day is usually prescribed, although greater effect is obtained for doses as high as 32 mg. The rationale for this use is that betahistine is said to increase circulation to the inner ear (Halmagyi, 1992) or affect vestibular function in some mysterious way through activity of H3 receptors (Kingma et al, 1997; Timmerman, 1994). At this writing, as H2 agonism would be stimulatory, it appears most likely that Serc acts through the H3 receptor. A recent review reported the mechanisms of action to include increasing vestibular blood flow and increasing the production and release of histamine within the brain (Lacour, 2001). The authors also noted the stumulatory effects on cerebral H1 receptors, which increases alertness. Serc is not approved as a drug by the FDA in the U.S — it is considered a placebo.; however, it can be obtained through compounding pharmacies. Histamine is sometimes prescribed as sublingual drops or subcutaneous injections. It is the authors opinion that sublingual or subcutaneous histamine is a placebo as it is rapidly degraded. Nevertheless, in the authors experience, Serc is moderately effective in suppressing symptoms of Meniere’s disease. Following the pharmacological discussion above, Serc might be expected to be effective in any peripheral vestibular disorder, not merely Meniere’s disease.

Steroids

Corticosteroids, such as Decadron, have been advocated for the treatment of Meniere’s disease and Vestibular neuritis, in an attempt to reduce the duration of a vertiginous episode. This use has not been studied formally. The author will occasionally use a few day course of Decadron (4 mg qd), when faced with a severe and unremitting vertigo attributed to Meniere’s disease.

Sympathomimetics

Sympathomimetics include ephedrine and the amphetamines. They may increase alertness and thereby counterbalance the sedative effects of vestibular suppressants. Sympathomimetics may also increase compensation. However, if used for this purpose, the combination of a vestibular suppressant with a drug targeted to increase compensation seems somewhat illogical. Amphetamines are little used because of their addiction potential.

Acetyleucine

This medication is marketed and largely used in France (Rascol et al, 1995). It is claimed to exert a rapid antivertiginous effect when administered intravenously in humans and also to act as a vestibular suppressant. It is not used in the U.S. for vertigo.

Tricyclid Antidepressants

Doxepin is a drug that has an H1 antagonist, adrenergic and antocholinergic properties. One small trial found it to be effective in preventing experimental vertigo in the lab. However, it has many side effects and interacts with a number of other medications, limiting its usefulness (Zajonc, 2006).

Serotonin Agonists

Fluoxetine (Prozac) and imipramine have been tested in animal models and found to be effective for the treatment of vertigo, but their effectiveness in humans is unclear (Zajonc, 2006).

Ginkgo Biloba

This extract is widely used in France, but its efficacy is in question (Rascol et al, 1995). It has been reported to suppress vertigo and to enhance vestibular compensation in animals. See here for more information.

Selective ACh Antagonists

The acetylcholine (ACh) receptor has numerous subtypes, and it would seem reasonable that a selective antagonist to the M2 receptor might cause vestibular suppression without many of the untoward side effects of the more general anti-ACh agents. Unfortunately, little research has been pursued in this direction at the present time.

Alternative Medicine Agents

Cocculus is advocated for the temporary relief of lightheadedness. Vertigoheel is also suggested for vertigo. Karkos et al performed a meta-analysis and found four clinical trials showing vertigoheel to be as effective in the treatment of vertigo as betahistine, ginko biloba, and dimenhydrinate.

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